Cyclophosphamide (CY) is the most extensively studied inhibitor of suppressor T lymphocyte (Ts) function. However, repeated administration of CY can abrogate sensitization. Therefore, we were interested in identifying noncytotoxic inhibitors of Ts function as adjuncts in the immunotherapy of Ts-inducing murine tumors. The effect of cimetidine (a histamine type 2 receptor antagonist) and diphenhydramine (a histamine type 1 receptor antagonist) on the Ts mediating tolerance to 2,4-dinitrofluorobenzene was studied. We report our data regarding the specific inhibition of Ts by cimetidine.